RESUMEN
BACKGROUND: Although urine drug testing can have vast legal and social ramifications, its interpretation during pregnancy and after birth remains not well understood. Fentanyl metabolism is altered by an individual's genetics, history of opioid use, and liver function. However, little is known about the clearance of fentanyl or its primary metabolite, norfentanyl, in the peripartum period. OBJECTIVE: We sought to identify and describe cases of delayed urine norfentanyl clearance in the pregnancy and postpartum period within our institution. STUDY DESIGN: This study described 3 cases of delayed urine norfentanyl clearance in pregnant and postpartum individuals in a colocated obstetrics, postpartum, and addiction medicine program. This program included prescriptions for medication for opioid use disorder and weekly urine drug testing with fentanyl immunoassay with reflex confirmation testing with liquid chromatography-tandem mass spectrometry for positive results with a limit of detection of 2.5 ng/mL. RESULTS: Low levels of norfentanyl (<16.3 ng/mL) were detected in urine 294 days, 126 days, and 231 days after the last fentanyl use. Patient self-reported abstinence was supported by consistently negative urine fentanyl levels throughout the collection period, compliant weekly urine drug tests that were otherwise only positive for buprenorphine, and negative fentanyl and norfentanyl in umbilical cord toxicology. CONCLUSION: Despite compliance in a medication for opioid use disorder program, the presence of norfentanyl in urine has significant consequences on the maternal-child dyad in the postpartum period. Caution should be used when using low levels of norfentanyl to determine an individual's abstinence, as it can lead to further discrimination against women in medication for opioid use disorder programs.
RESUMEN
Mice exposed in gestation to maternal high-fat/high-sucrose (HF/HS) diet develop altered bile acid (BA) homeostasis. We hypothesized that these reflect an altered microbiome and asked if microbiota transplanted from HF/HS offspring change hepatic BA and lipid metabolism to determine the directionality of effect. Female mice were fed HF/HS or chow (CON) for 6 wk and bred with lean males. 16S sequencing was performed to compare taxa in offspring. Cecal microbiome transplantation (CMT) was performed from HF/HS or CON offspring into antibiotic-treated mice fed chow or high fructose. BA, lipid metabolic, and gene expression analyses were performed in recipient mice. Gut microbiomes from HF/HS offspring segregated from CON offspring, with increased Firmicutes to Bacteriodetes ratios and Verrucomicrobial abundance. After CMT was performed, HF/HS-recipient mice had larger BA pools, increased intrahepatic muricholic acid, and decreased deoxycholic acid species. HF/HS-recipient mice exhibited downregulated hepatic Mrp2, increased hepatic Oatp1b2, and decreased ileal Asbt mRNA expression. HF/HS-recipient mice exhibited decreased cecal butyrate and increased hepatic expression of Il6. HF/HS-recipient mice had larger livers and increased intrahepatic triglyceride versus CON-recipient mice after fructose feeding, with increased hepatic mRNA expression of lipogenic genes including Srebf1, Fabp1, Mogat1, and Mogat2. CMT from HF/HS offspring increased BA pool and shifted the composition of the intrahepatic BA pool. CMT from HF/HS donor offspring increased fructose-induced liver triglyceride accumulation. These findings support a causal role for vertical transfer of an altered microbiome in hepatic BA and lipid metabolism in HF/HS offspring.NEW & NOTEWORTHY We utilized a mouse model of maternal obesogenic diet exposure to evaluate the effect on offspring microbiome and bile acid homeostasis. We identified shifts in the offspring microbiome associated with changes in cecal bile acid levels. Transfer of the microbiome from maternal obesogenic diet-exposed offspring to microbiome-depleted mice altered bile acid homeostasis and increased fructose-induced hepatic steatosis.
